Cefixime is a semi synthetic cephalosporin antibiotic for oral administration. It was first disclosed in U.S. Pat. No. 4,409,214 by Fujisawa Corporation, Japan. It is indicated for the treatment of infections caused by various gram—positive and gram—negative organisms chiefly uncomplicated urinary tract infections caused by E. coli and P. mirabilis, otitis media caused by H. influenza, M. catarrhalis and S. pyogenes, acute bronchitis and exacerbations of chronic bronchitis caused by S. pneumonia and H. influenza. It is also indicated for uncomplicated gonorrhea caused by N. gonorrhea. It is one of the most prescribed drugs for pediatric use.
Cefixime is currently available in a number of different formulations, for instance as oral suspension and tablets. Different formulations and different amounts of Cefixime are provided for adult and pediatric patients for example as tablets comprising 200 mg and 400 mg Cefixime trihydrate and as oral suspension comprising 100 mg/5 ml Cefixime trihydrate.
From the point of view of bioavailability, the preferred form of administration of sparingly soluble medicaments such as beta lactam antibiotics is often an aqueous suspension. However, there are limitations associated with this form of administration. For example, as mentioned in the product insert of “Suprax”, Cefixime, given orally, is about 40%-50% absorbed whether administered with or without food. The oral suspension, on the other hand, produces average peak concentrations approximately 25%-50% higher than the conventional tablets. The area under the time versus concentration curve is greater by approximately 10%-25% with the oral suspension than with the conventional tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. Thus, at the same dosage strength, Cefixime tablets are not bioequivalent to the suspension. Although suspensions are the common mode of administration of Cefixime especially to the pediatric population, they suffer from other disadvantages such as limited shelf life and lack of accuracy of dose measurement. The bitter taste of many such medicaments is also a drawback. The bulky nature of the container often precludes ease of carriage and storage.
Thus, a need exists for developing a formulation of Cefixime, which does not suffer from the disadvantages of the suspension formulation as elaborated above.
Solid dosage forms that are swallowed such as tablets and capsules provide accurate dosage, avoid taste problems and are more amenable to being portable; but since they have to disintegrate in the gastrointestinal tract and the medicament has then to dissolve before it can be absorbed, absorption tends to be slower than from a suspension and may be less than complete leading to bioequivalence issues as pointed out earlier. Also, some patients have difficulty in swallowing tablets and capsules, and there is a practical limit to the size, and therefore the dose, that can be swallowed. This is particularly true for geriatric patients and children.
Thus, the challenge for us was to formulate a dosage form comprising Cefixime, which would have a bioavailability similar to that of a suspension comprising Cefixime, but without the attendant disadvantages of suspension.